POS0103 IN RHEUMATOID ARTHRITIS, THE ASSOCIATION BETWEEN ANTI-MODIFIED PROTEIN ANTIBODIES AND LONG-TERM OUTCOMES IS DOMINATED BY THE EFFECT OF ANTI-CITRULLINATED PROTEIN ANTIBODIES
Authors: T. J. Van Wesemael, M. Verstappen, R. Knevel, A. Van der Helm-van Mil, T. Huizinga, R. Toes, D. Van der Woude
Journal: Annals of the Rheumatic Diseases (2022)

Background In rheumatoid arthritis (RA) many patients harbor autoantibodies against post translationally modified proteins (anti-modified protein antibodies (AMPA)): anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP) and anti-acetylated protein antibodies (AAPA). All three AMPA have been described to be associated with an increase in radiographic joint damage and ACPA also with a lower chance of obtaining sustained drugfree remission (SDFR). However, it is unclear whether the effects of these autoantibodies are independent of each other, and whether testing for all three AMPA offers additional information regarding these clinical outcomes. Objectives To investigate the individual and combined associations of AMPA with radiological progression and SDFR in RA. Methods In 612 RA patients from the Leiden Early Arthritis Clinic, we measured ACPA IgG with anti-CCP2-assays, anti-CarP IgG using homocitrullinated and native (as a control) fetal calf serum, and AAPA IgG by means of novel assays consisting of cyclic peptides with either acetylated or norleucine residues (as a control). Sharp-van der Heijde scores (SHS) were determined in 2685 sets of radiographs with yearly intervals for 7 years. The association of AMPA with SHS was assessed with a multivariate normal regression model. SDFR was defined as the absence of clinical synovitis after discontinuation of DMARD treatment. The association of SDFR with autoantibody-status was assessed with Kaplan-Meier curves. The very small number of patients single-positive for AAPA (n=4, 1%) precluded analyses in this subgroup. Results The prevalence of autoantibodies is shown in Table 1. A higher SHS was found in patients with autoantibodies compared to patients without antibodies, and in triple-positive versus single-positive patients (Figure 1A, p=0.04). To investigate if the higher SHS was due to the number of autoantibodies or a specific autoantibody, analyses were stratified for all three AMPAs. Interestingly, no difference was found in SHS between all ACPA-positive strata (Figure 1B). In the ACPA-negative stratum, a significant difference was found between patients with zero antibodies and solely anti-CarP (p=0.02). Table 1. Prevalence of autoantibodies in 612 rheumatoid arthritis patients in the EAC cohort Autoantibody status n (%) ACPA-positive 316 (52) Anti-CarP-positive 270 (44) AAPA-positive 208 (34) ACPA-AAPA-CarP- 255 (42) ACPA+ AAPA-CarP- 46 (7) ACPA- AAPA+ CarP- 4 (1) ACPA-AAPA- CarP+ 37 (6) ACPA+AAPA+ CarP- 37 (6) ACPA+ AAPA- CarP+ 66 (11) ACPA -AAPA+CarP+ - (0) ACPA+AAPA+CarP+ 167 (27) EAC: early arthritis clinic, ACPA: anti-citrullinated protein antibodies, anti-CarP/CarP: anti-carbamylated protein antibodies, AAPA: anti-acetylated protein antibodies The chance to obtain SDFR was lower in all antibody-positive groups compared to the autoantibody negative group. Moreover less triple-antibody-positive patients than single-antibody-positive patients achieved SDFR (P&lt;0.001), Figure 1C. After stratification for AMPA, no difference was found in the percentage of SDFR in all ACPA-positive strata, or in the ACPA-negative stratum, Figure 1D. Conclusion In ACPA-positive patients, the presence of other AMPA influences neither radiographic progression, nor the chance of SDFR. Thus, long-term clinical phenotype in RA is particularly dependent on the presence of ACPA, and less on the presence of other AMPA. Therefore, there appears to be no added value of testing the other AMPA for predicting clinical outcome in ACPA-positive patients. Disclosure of Interests None declared